Hereditary antithrombin deficiency in pregnancy – severe thrombophilic disorder as a danger for mother and foetus


Authors: Čápová Irena 1,2;  Salaj Peter 1;  Hrachovinová Rid 1
Authors‘ workplace: Centrum pro trombózu a hemostázu, Ústav hematologie a krevní transfuze, Praha 1;  Transfuzní a hematologické oddělení, Oblastí nemocnice Kolín a. s. 2
Published in: Ceska Gynekol 2021; 86(3): 175-182
Category:
doi: 10.48095/cccg2021175

Overview

Setting: In the article, we remember the role of antithrombin (AT) in hemostasis, escalation of AT-potential with heparin and difficulties with monitoring the effectiveness of LMWH therapy (low molecular weight heparin) in patients with AT deficiency. We pay most of our attention to hereditary AT deficiency and its thromboembolic risk in pregnancy.

Methods: In the introduction, the principle of AT function, its two main domains and the regulation of synthesis are cleared. We describe the causal mutations of hereditary AT deficiency in SERPINC1 gen and the relation to a thromboembolic risk. The general recommendations for patients with hereditary AT deficiency and pregnant women are mentioned. As the risk of thromboembolic disease is escalated in pregnancy, the LMWH should always be considered. There has been frequently observed that patients with AT deficiency do not elevate anti-Xa-levels when standard prophylactic LMWH doses are used. This fact well illustrates that heparin without AT may not inhibit the active coagulant factors efficiently enough. Therefore, if a high thromboembolic risk in the patient’s anamnesis is present, the LMWH dosing should be escalated. In individual cases, concomitant administration of an antithrombin concentrate to the heparin treatment is recommended at the time of delivery or in the case of deep venous thrombosis. In this article, three cases of unusual pregnancy in patients with different types of AT deficiency are reported. The case reports are summarized from the Department of Hematology at Hospital Kolín, the Centre of Hemostasis and Thrombosis at Institute of Hematology and Blood Transfusion in Prague and from cooperating obstetrical departments in the Czech Republic.

Results: We demonstrated the threat of hereditary AT deficiency in three case reports. In one case, the estimated risk of thromboembolism – type I of AT-deficiency (quantitative) – was in a good correlation with real peripartal complications. In the next two cases with different types of AT deficiency, we showed surprising courses of complicated pregnancies.

Conclusion: As it has been shown, it is not safe to estimate the risk of thromboembolism on the base of causal mutation for AT deficiency. For present clinical practice, we should still remember AT deficiency as a potentially very dangerous thromboembolic disorder for mother and fetus; thus, excellent cooperation of an obstetrician and a hematologist is necessary.

Keywords:

antithrombin – Heparin – antithrombin deficiency – gen SERPINC1 – Thromboembolism – antithrombotic prophylaxis – anti-Xa – aPTT – disseminated intravascular coagulopathy – consumptive coagulopathy


Sources

1. Van Cott EM, Orlando C, Moore GW et al. Recommendations for clinical laboratory testing for antithrombin deficiency. Communication from the SSC of the ISTH. J Thromb Haemost 2019; 18 (1): 17–22. doi: 10.1111/jth. 14648.

2. SÚKL. Anbinex, Grifols – SPC. 2021 [online]. Dostupné z: https: //www.sukl.cz/modules/medication/detail.php?code=0137484&tab=texts.

3. Maclean SP, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs 2007; 67 (10): 1429–1440. doi: 10.2165/00003 495-200767100-00005.

4. Matýšková M, Šlechtová M, Zavřelová J et al. Antitrombin. Transfuze Hematol dnes 2013; 19 (4): 244–249.

5. Di Minno MN, Ambrosino P, Ageno W et al. Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies. Thromb Res 2015; 135 (5): 923–932. doi: 10.1016/j.thromres.2015.03. 010.

6. Khor B, Van Cott EM. Laboratory tests for antithrombin deficiency. Am J Hematol 2010; 85 (12): 947–950. doi: 10.1002/ajh.21893.

7. Hajšmanová Z, Šlechtová J, Šigutová P et al. Průběh těhotenství při dlouhodobém podávání nízkomolekulárního heparinu pro opakované těhotenské ztráty. Ceska Gynekol 2008; 73 (5): 278–283.

8. Royal College of Obstetricians and Gynecologists. Thrombosis and embolism during pregnancy and the puerperium, reducing the risk (green-top guideline no. 37a). 2015 [online]. Available from: https: //www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/.

9. Tsikouras P, Christoforidou A, Bothou A et al. Ovecomming heparin resistance in pregnant women with antithrombin deificiency: a case report and review of the literature. J Med Case Rep 2018; 12 (1): 169. doi: 10.1186/s13256-018- 1711-2.

10. Croles FN, Lukens MV, Mulder R et al. Monitoring of heparins in antithrombin-deficient patients. Thromb Res 2019; 175: 8–12. doi: 10.1016/j.thromres.2019.01.007.

11. Pabinger I, Thaler J. How I treat patients with hereditary antithrombin deficiency. Blood 2019; 134 (26): 2346–2353. doi: 10.1182/blood. 2019002927.

12. Iba T, Gando S, Saitoh D et al. Antithrombin supplementation and risk of bleeding in patients with sepsis-associated disseminated intravascular coagulation. Thromb Res 2016; 145: 46–50. doi: 10.1016/j.thromres.2016.07.016.

13. Provazníková D, Matýšková M, Čápová I et al. Seventeen novel SERPINC1 variants causing hereditary antithrombin deficiency in a Czech population. Thromb Res 2020; 189: 39–41. doi: 10.1016/j.thromres.2020.02. 025.

14. Kearon C, Akl EA, Comerota AJ et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012; 141 (Suppl 2): e419S–e494S. doi: 10.1378/chest.11-2301.

15. Durai S, Tan LK, Lim S. Antithrombin deficiency in pregnancy. BMJ Case Rep 2016; 2016: bcr2015213310. doi: 10.1136/bcl-2015-213310.

16. Refaei M, Xing L, Lim W et al. Management of venous thromboembolism in patients with hereditary antithrombin deficiency and pregnancy: case reports and review of the literature. Case Rep Hematol 2017; 2017: 9261351. doi: 10.1155/2017/9261351.

17. Biron-Andréani C. Venous trombembolic risk in postpartum. Phlebolymphology 2013; 20 (4): 167.

18. Robertson L, Wu O, Langhorne P et al. Trombophilia in pregnancy: a systematic review. Br J Haematol 2006; 132 (2): 171–196. doi: 10.1111/j.1365-2141.2005.05847.x.

19. Bates SM, Rajasekhar A, Middeldorp S et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv 2018; 2 (22): 3317– –3359. doi: 10.1182/bloodadvances.2018024 802.

20. James AH, Konkle BA, Bauer KA. Prevention and treatment of venous thrombembolism in pregnancy in patients with hereditary antithrombin deficiency. Int J Womens Health 2013; 5: 233–241. doi: 10.2147/IJWH.S43190.

Labels
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine
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